PURPOSE: Comprehensive genomic profiling (CGP) assay is increasingly used in low-middle–income countries to detect clinically relevant genomic alterations despite its clinical benefits not being well known. Here, we describe the proportion of patients with advanced cancer in India who received targeted therapy for an actionable genetic alteration identified on CGP assays. METHODS: This was a multicenter, retrospective cohort study in adult patients with advanced nonhematologic malignancies who underwent a CGP test. If patients received a targeted therapy for ≥ 6 months, they were considered to have obtained a clinical benefit from the medication, whereas those continuing for ≥ 12 months were considered to have attained an exceptional response. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy. RESULTS: During 2019-2020, 12 medical oncologists provided CGP reports for 297 patients; 221 met the inclusion criteria. Patients received a median of two lines (range: 0-5) of prior systemic therapy. On the basis of the CGP assay, 21 patients (10%) received targeted therapy. Among them, 33% was for human epidermal growth factor receptor 2 (HER2) amplification (nonbreast cancer) and 19% for HER2 or epidermal growth factor receptor exon 20 insertion mutation (lung cancer). After excluding patients with HER2 or epidermal growth factor receptor exon 20 insertions, 8% of 217 patients received targeted therapy. In the overall cohort of 221 patients, clinical benefit was seen in nine patients (4%), of whom two were exceptional responders (1%). CONCLUSION: We observed that in a low-middle–income country setting, 10% of patients received targeted therapy on the basis of CGP assay. Only 4% of patients who underwent CGP testing obtained a clinical benefit.

Ovarian cancer (OC) is one of the most lethal gynecological cancers with a 5-year survival rate that ranges from 30% to 40%. Breast cancer genes (BRCA1 and BRCA2) play a key role in maintaining genomic stability. Mutations in BRCA1/2 genes lead to the accumulation of double-strand breaks, resulting in tumorigenesis. The risk of developing OC in women with BRCA1 and BRCA2 mutations is 39% and 11%, respectively, by 70 years of age. BRCA1/2 mutation testing is thus important to identify women at greatest risk of developing OC in addition to its impact on diagnosis, prognosis, and targeted therapy. Genetic testing is required to identify the BRCA mutations and thus select patients who can benefit from polyadenosine diphosphate (ADP)–ribose polymerase (PARP) inhibitor therapy. Tumor BRCA mutation testing can detect both germline and somatic mutations allowing implementation of preventive strategies on a broader population. Various international guidelines recommend BRCA1/2 mutation genetic testing in all OC patients irrespective of age and family history. This review focuses on the role of BRCA mutation testing in OC.

Background & objectives: Gallbladder (GBC) is an aggressive form of cancer and most patients present with advanced unresectable disease due to lack of early signs and symptoms. This retrospective study was conducted to present the treatment outcomes with three lines of chemotherapies in a subset of patients with advanced, unresectable GBC with the primary objective to determine the response rates with nab-paclitaxel as the third-line chemotherapy after failure of the first-line gemcitabine and platinum and the second-line FOLFOX-4 (oxaliplatin, leucovorin and 5-FU) therapy. Another objective was to evaluate the toxicity, progression-free survival (PFS) and overall survival (OS). Methods: Treatment-naive patients with histologically proven inoperable GBC treated with gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel as the first-, second- and third-line chemotherapy were included in this study. The dose of gemcitabine and cisplatin or carboplatin was 1 g/m² on days 1 and 8 and 75 mg/m² (or target AUC of 5) on day 1, in a 21-day cycle. FOLFOX-4 was administered every two weeks and nab-paclitaxel was administered as 125 mg/m² on days 1, 8 and 15 in a 28-day cycle. Results: There were eight men and 13 women with a median age of 57 yr who received nab-paclitaxel therapy. The overall response rate of the first-, second- and third-line chemotherapy was 61.9, 57.1 and 52.4 per cent, respectively. The median PFS for the gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel therapy was 5.5, 5.4 and 2.9 months, respectively. The median OS with three lines of therapies was 14.0 months. Common Terminology Criteria (CTC) grade 3 or 4 haematological toxicities were observed in 28.6, 38.1 and 23.8 per cent of patients on gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel therapy, respectively. Interpretation & conclusions: Our study suggests the clinical benefit of nab-paclitaxel chemotherapy in prolonging OS in a selected subgroup of advanced, unresectable GBC patients after failure of the first-line gemcitabine and platinum and the second-line FOLFOX-4 therapy.

Artificial intelligence (AI) has become an essential tool in human life because of its pivotal role in communications, transportation, media, and social networking. Inspired by the complex neuronal network and its functions in human beings, AI, using computer-based algorithms and training, had been explored since the 1950s. To tackle the enormous amount of patients' clinical data, imaging, histopathological data, and the increasing pace of research on new treatments and clinical trials, and ever-changing guidelines for treatment with the advent of novel drugs and evidence, AI is the need of the hour. There are numerous publications and active work on AI's role in the field of oncology. In this review, we discuss the fundamental terminology of AI, its applications in oncology on the whole, and its limitations. There is an inter-relationship between AI, machine learning and, deep learning. The virtual branch of AI deals with machine learning. While the physical branch of AI deals with the delivery of different forms of treatment—surgery, targeted drug delivery, and elderly care. The applications of AI in oncology include cancer screening, diagnosis (clinical, imaging, and histopathological), radiation therapy (image acquisition, tumor and organs at risk segmentation, image registration, planning, and delivery), prediction of treatment outcomes and toxicities, prediction of cancer cell sensitivity to therapeutics and clinical decision-making. A specific area of interest is in the development of effective drug combinations tailored to every patient and tumor with the help of AI. Radiomics, the new kid on the block, deals with the planning and administration of radiotherapy. As with any new invention, AI has its fallacies. The limitations include lack of external validation and proof of generalizability, difficulty in data access for rare diseases, ethical and legal issues, no precise logic behind the prediction, and last but not the least, lack of education and expertise among medical professionals. A collaboration between departments of clinical oncology, bioinformatics, and data sciences can help overcome these problems in the near future.

S-1 (5-fluorouracil prodrug [tegafur] in combination with 5-chloro-2,4-dihydroxypyridine [CDHP] and potassium oxonate [OXO]) was first approved in 1999. In order to make it easy for community oncologists, we decided to put together this expert consensus guideline for its use in gastrointestinal (GI) malignancies. A total of 15 subject matter experts used modified Delphi method to discuss, analyze, and vote on key aspects regarding practical approach to use of S-1 in GI cancers, a process involving 6 months of work. The consensus guidelines specify how S-1 use can be optimized in patients with colorectal, gastric, and pancreatic tumors. The voting for the 17 key points resulted in a majority consensus for all the statements (approval ranging from 13/15 [87%] to 15/15 [100%]). S-1 is a combination of three drugs (tegafur, CDHP, and OXO) specifically designed to reduce toxicity and enhance efficacy; clinical data and meta-analysis confirm both factors; and it is recommended as standard of care for GI cancers. S-1 is approved and one of the standards of care for all lines of therapy in colorectal cancer and pancreatic cancers. S-1 with oxaliplatin is the standard of care for gastric cancers.

PURPOSE: Immune checkpoint inhibitors (ICIs) is the initial line of management in advanced hepatocellular carcinoma (HCC), but survivals in the real world are not known. MATERIALS AND METHODS: A retrospective study of patients with advanced HCC receiving ICIs (as first-line therapy or as later lines of therapy) across 11 Indian institutions was conducted. Patients were divided into either cohort 1 (trial-like receiving ICI as first-line therapy), with a Child Pugh score (CTP) of ≤6, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1, and no VP4 (main portal vein thrombosis [MPVT]) or cohort 2 (trial unlike) who did not satisfy at least one of the above criteria. The primary end point was 12-month overall survival (OS). RESULTS: Between January 2017 and January 2022, 133 patient data were analyzed. The presence of MPVT was seen in 33 patients (25%). The ICIs used were atezolizumab-bevacizumab, nivolumab, and pembrolizumab in 89 (66%), 44 (33%), and one (1%) patients, respectively. With a median follow-up of 13.8 months, the 12-month OS for the entire cohort was 33.4% (95% CI, 23.6 to 43.2). Patients in cohort 1 (n = 31) had a significantly improved OS compared with patients in cohort 2 (n = 102; 12-month OS, 57.9% [95% CI, 38.5 to 77.3] v 24% [95% CI, 13.4 to 34.6]; P = .005). Patients with CTP A as compared with CTP B (9.7 v 4.3 months; P < .001) and an ECOG PS of 0/1 as compared with a PS of ≥2 (8.7 v 7.2 months; P = .04) and without MPVT (9.4 v 4.0; P < .001) had superior survivals. CONCLUSION: Patients with advanced HCC in the real world, trial-like have survivals in consonance with trial data, whereas patients with features excluding them from trials, such as main portal vein thrombosis, poor ECOG PS, and child Pugh B status, have markedly inferior survivals, despite good tolerance to immunotherapy.